Summary of Evidence

Published studies of gastric electrical stimulation (GES) for the treatment of gastroparesis and other conditions have been generally inconclusive and of poor quality. However, gastroparesis symptom improvement and short-term weight loss in some patients has been reported. The American College of Gastroenterology (ACG) practice guideline suggests that GES may be considered for compassionate treatment in patients with refractory symptoms, particularly nausea and vomiting due to gastroparesis. No support from specialty societies for GES to treat diabetes or obesity was found. GES may be considered appropriate as a compassionate use treatment of severe, refractory gastroparesis. This treatment is considered investigative for all other conditions, including diabetes without gastroparesis and obesity, due to the lack of evidence demonstrating an impact on improved health outcomes. 

Rationale

Gastric electrical stimulation (GES) using an implantable device has been investigated primarily as a treatment for gastroparesis. Gastroparesis is a chronic disorder of gastric motility characterized by delayed emptying of a solid meal. Symptoms include bloating, distension, nausea, and vomiting. When severe and chronic, gastroparesis can be associated with dehydration, poor nutritional status, and poor glycemic control in diabetic patients. While most commonly associated with diabetes, gastroparesis is also found in chronic pseudo-obstruction, connective tissue disorders, Parkinson’s disease, and psychological pathologic conditions. Some cases may be idiopathic.

Treatment of gastroparesis includes prokinetic agents (e.g., metoclopramide) and antiemetic agents (e.g., diphenhydramine, ondansetron, prochlorperazine). Severe cases may require enteral or total parenteral nutrition. UpToDate describes a treatment algorithm to manage gastroparesis based on severity of delayed gastric emptying. After initial steps involving dietary modification and nutritional support, trials of several classes of prokinetics and antiemetics are recommended before consideration of compassionate use gastric electrical stimulation or surgical therapy.

GES has also been investigated as a treatment of obesity. It is used to increase a feeling of satiety with subsequent reduction in food intake and weight loss. The exact mechanisms resulting in changes in eating behavior are uncertain but may be related to neurohormonal modulation and/or stomach muscle stimulation. Currently, no GES devices have been approved by the FDA for the treatment of obesity.

Gastric Electrical Stimulation for Gastroparesis

FDA approval was granted based on a small randomized controlled trial (WAVESS, n=33) and a small compassionate use study (n=18) of safety and efficacy. The study was reported by Abell et al in 2003 and is also described in the FDA label for the Enterra^™ Therapy System. In the WAVESS trial, patients with drug-refractory gastroparesis of diabetic or idiopathic etiologies were evaluated in a double-blind, randomized cross-over study over a 12-month period. Entry criteria included symptomatic gastroparesis > 1 year, as documented by an initial gastric emptying test, refractory or intolerance to at least two anti-emetic and prokinetic drug classes, stable medical therapy, vomiting frequency of > 7 episodes per week, and delayed gastric emptying measurements. Results indicated that, although there was no difference in the vomiting frequency with stimulation ON or OFF during the 2-month crossover phase, 21 subjects preferred the device ON while 7 preferred the device OFF. Five had no preference. The results of secondary endpoint evaluations indicated that many patients experienced improvements in quality of life (73%) and ability to tolerate solid meals (73%).

Hayes, Inc, an organization that focuses on evidence-based assessments of health technologies,  completed a Health Technology Assessment report on GES for gastroparesis in 2018 which was updated in 2022. A review of the medical literature identified 12 studies that evaluated GES for gastroparesis: 3 randomized crossover trials, 6 pretreatment/posttreatment studies (7 publications), 1 nonrandomized comparative study, 1 comparative cohort study, and 1 compilation of case series. Results of these studies are inconsistent, resulting in a ‘C’ rating for gastric electrical stimulation as an adjunct to standard care for the treatment of gastroparesis refractory to medical therapy in adult patients. According to Hayes, this rating reflects low-quality evidence consisting of positive findings from nonrandomized studies without blinding and inconclusive results from 3 randomized studies that involved blinding. Cross-over studies indicated that patients generally reported improvement in symptoms at follow-up whether or not the device was turned on, suggesting a placebo effect. The large body of evidence, rated from poor to fair quality, suggest that GES may relieve gastroparesis symptoms and improve gastric emptying and health-related quality of life in some patients with medically refractory gastroparesis. Although GES is safe in most patients, serious complications can occur that are predominantly related to stimulator implantation and shifting of the stimulator or its electrical leads after implantation. 

Gastric Electrical Stimulation for Obesity

In 2014, Cha et al reported a systematic review on gastric electrical stimulation to treat obesity. Thirty-one studies, consisting of a total of 33 primarily small, non-randomized trials were included in the data analysis. Weight loss was achieved in most studies, especially during the first 12 months, but only very few studies had a follow-up period longer than 1 year. The author concluded that many studies have demonstrated that GES is effective for short-term weight control as well as for the change of other variables associated with obesity, although results are inconsistent. Well-designed, standardized clinical trials with a larger sample size and a longer follow-up period should be considered to prove its true benefit for the treatment of obesity and further advancement in GES device technology is needed. 

In 2016, Lebovitz published a review article on gastric electrical stimulation as an interventional treatment of obesity and diabetes. Results of studies of a gastric pacemaker device, a vagal blockade device, and a multi-electrode non-excitatory prandial gastric electrical stimulation device are reported. The author concludes that gastric electrical stimulation for effectively treating moderate obesity has remained elusive. He further reports that combining lifestyle modifications with GES frequently complicates the interpretation of results.

The only prospective, randomized, placebo-controlled, double-blind trial found in the published literature of GES for the treatment of obesity is the SHAPE trial reported by Shikora et al in 2009. Patients required a BMI of ≥ 35 to qualify. All 190 patients participating in the trial received an implantable gastric stimulator and were randomized to have the stimulator turned on or off. All patients were evaluated monthly, participated in support groups, and reduced their dietary intake by 500 kcal/d. At 12-month follow-up, there was no statistically significant difference in weight loss between the treatment group (weight loss, 11.8%) and the control group (weight loss, 11.7%) using intention-to-treat analysis (p=0.717).

Practice Guidelines and Position Statements

The American College of Gastroenterology (ACG) published clinical practice guidelines on management of gastroparesis (GP) in 2013. ACG recommended that:

• GES may be considered for compassionate treatment in patients with refractory symptoms, particularly nausea and vomiting. Symptom severity and gastric emptying have been shown to improve in patients with diabetic gastroparesis, but not in other types of gastroparesis.

In 2022, the ACG published an update to these guidelines, noting that documented clinical usefulness in both idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) suggests there is a role for GES in accordance with its HUD approval:

• Gastric electric stimulation (GES) may be considered for control of GP symptoms as a humanitarian use device (HUD) (conditional recommendation, low quality of evidence).

The American Diabetes Association published Standards of Medical Care in Diabetes in 2024. The ADA acknowledges that treatment for diabetic gastroparesis may be very challenging; various diet and pharmacological treatment strategies to manage this condition are described. The ADA also notes that gastric electrical stimulation using a surgically implantable device has received approval from the FDA, although there are very limited data in diabetic peripheral neuropathy (DPN) and the results do not support gastric stimulation as an effective therapy in diabetic gastroparesis.

Reference List

1. Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology. 2003;125(2):421-428. doi:10.1016/s0016-5085(03)00878-3.
2. American Diabetes Association Professional Practice Committee. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S231-S243. doi:10.2337/dc24-S012.
3. Camilleri M. Gastroparesis: Etiology, clinical manifestations, and diagnosis. UpToDate, Inc. June 2024. Wolters Kluwer Health, Philadelphia, PA. 
4. Camilleri M, Kuo B, Nguyen L, et al. ACG Clinical Guideline: Gastroparesis. Am J Gastroenterol. 2022;117(8):1197-1220. doi:10.14309/ajg.0000000000001874.
5. Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L; American College of Gastroenterology. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108(1):18-38. doi:10.1038/ajg.2012.373
6. .Cha R, Marescaux J, Diana M. Updates on gastric electrical stimulation to treat obesity: Systematic review and future perspectives. World J Gastrointest Endosc. 2014;6(9):419-431. doi:10.4253/wjge.v6.i9.419.
7. FDA approval letter HDE H990014, Gastric Electrical Stimulator (GES) system (now called Enterra^™), Medtronic, 2000. https://www.accessdata.fda.gov/cdrh_docs/pdf/H990014A.pdf.
8. FDA labeling. Enterra^™ Therapy 4301. Medtronic, 2000. https://www.accessdata.fda.gov/cdrh_docs/pdf/H990014C.pdf.
9. Hayes, Inc. Gastric Electrical Stimulation for Gastroparesis Health Technology Assessment report, October 26, 2018. Annual Review: December 7, 2022. Hayes, Inc., a Symplr company, Houston, TX.
10. Lebovitz HE. Interventional treatment of obesity and diabetes: An interim report on gastric electrical stimulation. Rev Endocr Metab Disord. 2016;17(1):73-80. doi:10.1007/s11154-016-9350-7.
11. Marathe PH, Gao HX, Close KL. American Diabetes Association Standards of Medical Care in Diabetes 2017. J Diabetes. 2017;9(4):320-324. doi:10.1111/1753-0407.12524.
12. McCallum RW, Sarosiek I, Parkman HP, et al. Gastric electrical stimulation with Enterra therapy improves symptoms of idiopathic gastroparesis. Neurogastroenterol Motil. 2013;25(10):815-e636. doi:10.1111/nmo.12185.
13. McCallum RW, Snape W, Brody F, Wo J, Parkman HP, Nowak T. Gastric electrical stimulation with Enterra therapy improves symptoms from diabetic gastroparesis in a prospective study. Clin Gastroenterol Hepatol. 2010;8(11):947-e116. doi:10.1016/j.cgh.2010.05.020.
14. Shikora SA, Bergenstal R, Bessler M, et al. Implantable gastric stimulation for the treatment of clinically severe obesity: results of the SHAPE trial. Surg Obes Relat Dis. 2009;5(1):31-37. doi:10.1016/j.soard.2008.09.012.